The overarching goal of this project is to develop a new approach to capturing information about the three- dimensional structure of fluorescent samples. The hardware we develop will be able to capture this information without specialized optics, or indeed without any optical apparatus at all beyond an LED and our chip. As such, this technology has the capacity to reduce the size and cost of imaging-based assays by orders of magnitude. Deployed as part of highly parallel and/or portable instruments, this sensor will dramatically expand the types and amounts of useful data that can be gathered. The specific aims of this project, discussed below, are: 1) development of novel opto-electronic hardware (a CMOS chip) using existing, scalable semiconductor manufacturing;2) development of data-processing tools for the reconstruction of fluorescent structure from chip output;3) demonstration of this system for both static and dynamic imaging of fluorescent cells or tissue;and 4) provision of a unique research experience for scientist- engineers in training. The key element that will enable chip-scale lensless imaging is an angle-sensitive pixel manufactured entirely in CMOS. Such a pixel has been demonstrated by the PI's lab, detecting not only light intensity, but also its incident angle. These pixels make use of near-field diffraction patterns generated and filtered by local gratings to only pass light at certain incident angles. This light is detected by local photodiodes, just as in a normal CMOS imager. By combining multiple sub-pixels with different preferred angles, one can construct a full angle-sensitive pixel that is of a similar scale to pixels in existing imagers. The gratings are constructed using the metal wiring layers present in any modern semiconductor process, and the photodiodes use standard semiconductor junctions. Thus arrays of angle-sensitive pixels can be constructed entirely using existing CMOS manufacturing processes identical to those used to build other integrated circuits and imagers. Such chips, can be manufactured at extremely low cost (<$5 apiece) providing a massive reduction in the cost and size of image-based assays. Simulations of arrays of angle-sensitive pixels indicate that they will be able to localize multiple fluorescent sources such as GFP tagged cells distributed in 3-d space. We will design such arrays (to be manufactured through MOSIS) and deploy them in simple micro-fluidic packages to demonstrate their utility in imaging cell and tissue cultures and in high-throughput flow cytometry. Our final goal is to build a centimeter-scale instrument able to image the three-dimensional structure of a fluorescent sample at high frame rates with a manufacturing cost of less than $10. PUBLIC HEALTH RELEVANCE: The goal of this project is to develop very small, very cheap instrument able to image the three- dimensional structure of a biological sample, replacing microscopes for many applications. This capability would enable filed-deployable imaging systems for doctors and scientists away from the lab. Also because of its low cost and small size, this instrument will enable massive parallelization of imaging-based assays, enabling fast screening of large numbers of tissue samples or cell cultures in, for example, drug discovery.